Uterine Leiomyomas: Options and Choices

Uterine leiomyomas are benign smooth muscle tumors that occur in up to 50% of women during their reproductive years. They are a frequent cause of abnormal uterine bleeding, pelvic pain, reduced fertility, and miscarriage. Current medical treatments for leiomyomas involve the temporary suppression of serum estradiol or progesterone by the use of gonadotropin-releasing hormone agonists or the progesterone antagonist RU-486. These medications are currently limited to short-term use because of their side effects related to steroid suppression (bone loss, adverse effects on lipids, impaired cardiovascular and/or neurological function). As a result, surgical treatments such as hysterectomy or myomectomy are generally required for patients presenting with significant symptoms. According to the National Center for Health Statistics, 10 to 15% of all women between the ages of 25 to 64 will eventually require surgery as a consequence of this disease. In the United States alone, uterine leiomyomas are cited as the primary indication for hysterectomy in over 250,000 cases per year, accounting for well over $2.5 billion in health care expenditures. Therefore, development of safe and effective nonsurgical, minimally invasive, or preventative therapies for leiomyomas would provide tremendous health benefits for women.

The development of new options for patients in the future will certainly be based on a better understanding of the genetics and molecular biology of uterine leiomyomas. Dr. James Segars highlights the great potential of gene array studies as a powerful tool to identify unique or currently overlooked genes that may play a critical role in the development and progression of uterine leiomyomas. This work and studies to come in this area will be an important foundation for the development of medical and gene therapy approaches in the future.

Dr. John Stribley reviews prior studies and outlines future directions in understanding why apoptosis is defective in uterine leiomyomas. Tumor progression is an imbalance of cell proliferation versus apoptosis. A shift in this imbalance by the promotion of apoptosis may enhance current therapies focused on the inhibition of steroid-induced cell proliferation.

Dr. Cheryl Walker and Dr. Kristof Chwalisz highlight the background and current status of hormonal approaches to treat uterine fibroids, looking at the roles of estrogen and progesterone, respectively. Dr. Walker is a pioneer in defining the actions and cellular mechanisms of estrogen and antiestrogens in leiomyomas and pioneered the development of a unique estrogen-responsive leiomyoma cell line currently utilized by many investigators around the world. Dr. Kristof Chwalisz highlights the history and development of a unique selective progesterone modulator that shows great promise as a new medical approach to the treatment of women with uterine leiomyomas presenting with menorrhagia.

Dr. Steven Young highlights and reviews the potential of nonhormonal therapies for the treatment of uterine leiomyomas. Although current therapies for fibroids are generally reserved for the symptomatic patient, nonhormonal medical options may play a future role in suppressing the growth of uterine leiomyomas in women identified with asymptomatic myomas.

The final three authors highlight new minimally invasive interventions for the treatment of fibroids in women wishing to preserve their uterus. Dr. Ruth Carlos discusses the current limitations and strengths of various imaging modalities for the management of uterine leiomyomas. In addition, Dr. Carlos discusses the present role and indications and contraindications for vascular embolization therapy for uterine leiomyomas including the risks of ovarian failure and catheter-related injury. Dr. Bryan Cowan reviews his data on the use of real-time magnetic resonance imaging of the uterus to direct cryotherapy of uterine fibroids in a minimally invasive manner. Dr. Advincula highlights the current technology, controversies, and future of endoscopic management of uterine fibroids.

In the past, women were given few options for the treatment of uterine leiomyomas. We will soon evolve from a woefully short option list of hysterectomy versus waiting with anxiety to a multitude of choices that may be applied taking into account each patient's unique desires and future goals. All authors have presented their subject manner in a comprehensive and evidence-based manner. I am confident that the readers will appreciate the value of this timely review and enjoy the hard work of the authors. I am grateful to the authors for sharing their time, insights, and enthusiasm in making this project and special volume a reality.